Field of the Invention
The invention in general relates to cancer therapeutics. More specifically, the present invention relates to the ability of (E)-1-(3′, 4′-Dimethoxyphenyl) butadiene [DMPBD] to exert anti-tumorigenic and anti-metastatic activity.
Description of Prior Art
It is well known that chronic inflammation increases the risks of cancer and eliminating inflammation reduces the risk for cancer development. Hence anti-inflammatory agents are encouraged to be used in tandem (as adjuvants) with chemotherapeutic agents wherein these anti-inflammatory agents exert their activity by reducing toxicity of associated chemotherapy, by altering the pharmacokinetics chemotherapeutics resulting in better efficacy and due elimination and also by sensitising cancerous cells to chemotherapy itself (Elizabeth R. Rayburn et al, “Anti-inflammatory agents for cancer chemotherapy”, Mol Cell Pharmacol. 2009; 1 (1): 29-43. It is also known from prior art that anti-inflammatory substances can also have anti-cancer effects. For example, Nonsteroidal anti-inflammatory drugs (NSAIDS induce apoptosis in various cancer cells. Despite many suggested mechanisms for the anti-cancer effect of NSAIDS including cyclooxygenase inhibition, reactive oxygen species inhibition, and NF-κB mediated signal inhibition, it remains uncertain how they induce cell cycle arrest and apoptosis in cancer cells. In other words, there is little information on the selectivity of anti-inflammatory agent mediated anti-cancer effects although this information is very critical for successful anti-cancer therapy and future cancer therapeutic advances (M. Adachi et al, “Nonsteroidal anti-inflammatory drugs and oxidative stress in cancer cells”, Histol Histopathol (2007) 22: 437-442). Thus, the prediction of the direct effect of such anti-inflammatory molecules in cancer growth or metastasis is difficult (Laurie E Walker, “NSAIDS as anticancer drugs”, in clinician's brief) and needs considerable scientific evaluation. The anti-inflammatory properties of (E)-1-(3,4-dimethoxyphenyl) butadiene (DMPBD) is well known from prior art (Jeenapongsa et al, “Anti-inflammatory activity of (E)-1-(3,4-dimethoxyphenyl) butadiene from Zingiber cassumunar Roxb.”, J Ethnopharmacol. 2003 August;87(2-3):143-8), Also, the efficacy o the trans dimer of DMPBD namely, (+/−) trans-3-(3′, 4′-dimethoxyphenyl)-4-[(E)-3′″, 4′″-dimethoxy-styryl] cyclohex-1-ene has been discussed in terms of its antiproliferative effects in lung cancer (Journal of Pharmacognosy and Phytochemistry 2015; 4(1): 01-06).
The present inventors for the first time demonstrate the concentration dependant in-vitro anti-tumorigenic activity of (E)-1-(3,4-dimethoxyphenyl) butadiene on cancer cell lines PANC-1 (pancreatic carcinoma), DU-145 (prostate carcinoma) and SKOV3 (ovarian carcinoma) through cell proliferation assays. Further, the unique ability of DMPBD to cause significant fold decrease in the expression of cell adhesion molecules (P-selectin, E-selectin and L-selectin) as evaluated by flow cytometric studies on pancreatic carcinoma cells points to the molecule's specific function as an anti-metastatic agent. Important prior art emphasising the role of selectins in tumor metastasis include.                a. H. Laubli et al, “Selectins promote tumor metastasis”, Semin Cancer Biol. 2010 June; 20 (3): 169-77;        b. Hariri. G et al, “Radiation guided P-selectin antibody targeted to lung cancer”, Ann Biomed Eng. 2008 May; 36 (5): 821-830;        c. Chen M et al, “P-selectin mediates adhesion of leucocytes, platelets and cancer cells in inflammation, thrombosis, cancer growth and metastasis”, Arch Immunol Ther Exp (Warsz). 2006 March-April; 54 (2): 75-84; and        d. Okegawa T et al, “The role of cell adhesion molecule in cancer progression and its application in cancer therapy”, Acta Biochim Pol. 2004; 51 (2) 445-57.        
These scientific developments are important given that cancer therapy objective depends on    1. Specificity of chemotherapeutic agent to a particular cancer type; and    2. Twin efficacy of said agent in preventing undue cell proliferation and also tumor metastasis.
The inventive features of the present invention as elucidated above clearly fulfill the aforesaid objectives by demonstrating the anti-tumorigenic specificity of DMPBD for pancreatic, ovarian and prostate carcinomas and also the ability of DMPBD to prevent spread or metastasis of these carcinomas or others by inhibition of cell adhesion molecules p-selectin, E-selectin and L-selectin thus providing novel and non-obvious technical information useful for chemotherapy of pancreatic, ovarian and prostate cancers and prevention of metastasis thereof.